POWER CALCULATIONS

(1)

POWER CALCULATIONS

Below are listed power calculations for all primary and secondary outcomes

Spot sign positive Spot sign negative

Primary continuous

outcome Approximate number of patients available:

54 (27 in each allocation group). We have assumed that 10% will have missing day-2 CTC.

We assume that the absolute haematoma expansion volume within each group is normally distributed with a standard deviation of 17 mL. We also assume that the true mean difference is 14 mL.[1]

Probability of rejecting the null hypothesis (power) .844.

Approximate number of patients available:

162 (81 in each allocation group). We have assumed that 10% will have missing day-2 CTC.

We assume that the absolute haematoma expansion volume within each group is normally distributed with a standard deviation of 8 mL. We also assume that the true mean difference is 2 mL.[1]

Secondary composite

binary outcome Approximate number of patients available:

60 (30 in each allocation group).

We assume an event-rate in the control- population of 50%.[2] We also assume a RRR of 40%.

We assume an event-rate in the control- population of 10%.[2] We also assume a RRR of 40%.

Probability of rejecting the null hypothesis (power) .167

Serious adverse events

within the first 7 days Approximate number of patients available:

We assume an event-rate in the control population of 50%. We also assume a RRI of 20%.

Safety outcome within the

first 90 days Approximate number of patients available:

Thromboembolic events

within the first 90 days Approximate number of patients available:

We assume an event-rate in the control population of 10%.[3] We also assume a RRI of 20%.

(2)

Probability of rejecting the null

hypothesis (power) .057. Probability of rejecting the null hypothesis (power) .071.

90-day functional outcome (modified Rankin Scale) - dichotomised

We assume an event-rate in the control- population of 70%. [4,5] We also assume a RRR of 20%.

Probability of rejecting the null hypothesis (power) .200

We assume an event-rate in the control- population of 50%. [4,5] We also assume a RRR of 20%.

90-day functional outcome (Barthel index) -

continuous

As no previous study using the CTA-based spot sign has published data on Barthel- index, reliable power-calculation could not be conducted.

90-day survival outcome Approximate number of patients available:

60 (30 in each allocation group). We estimate an accrual interval of 1 time units and additional follow-up after the accrual interval of 89 time units.

In a previous study, the median survival time on the control treatment was

approximately (extrapolated[6]) 174.9 time units.[2]

We assume a true hazard ratio of control subjects relative to experimental subjects is 0.8,

180 (90 in each allocation group). We estimate an accrual interval of 1 time units and additional follow-up after the accrual interval of 89 time units.

In a previous study, the median survival time on the control treatment was approximately (extrapolated[6]) 384.0 time units.[2]

We assume a true hazard ratio of control subjects relative to experimental subjects is 0.8,

For all power-calculations above, a probability of type 1 error of 5% is assumed. For dichotomous

outcomes, power is calculated based on uncorrected chi

²

-test. Power-calculation was conducted

using PS: Power and Sample size calculation version 3.1.2, 2014.[7] mL – millilitre; RRR – relative

risk reduction; RRI – relative risk increase.

(3)

SUPPLEMENTARY REFERENCES:

1 Wada R, Aviv RI, Fox AJ, Sahlas DJ, Gladstone DJ, Tomlinson G, Symons SP: Ct angiography "spot sign" predicts hematoma expansion in acute intracerebral hemorrhage. Stroke 2007;38:1257-1262.

2 Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, Molina CA, Blas YS, Dzialowski I, Kobayashi A, Boulanger JM, Lum C, Gubitz G, Padma V, Roy J, Kase CS, Kosior J, Bhatia R, Tymchuk S, Subramaniam S, Gladstone DJ, Hill MD, Aviv RI, group PRSICs: Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the ct-

angiography spot sign (predict): A prospective observational study. Lancet Neurol 2012;11:307- 314.

3 Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T, Investigators FT: Efficacy and safety of recombinant activated factor vii for acute intracerebral hemorrhage. N Engl J Med 2008;358:2127-2137.

4 Delgado Almandoz JE, Yoo AJ, Stone MJ, Schaefer PW, Oleinik A, Brouwers HB, Goldstein JN, Rosand J, Lev MH, Gonzalez RG, Romero JM: The spot sign score in primary intracerebral hemorrhage identifies patients at highest risk of in-hospital mortality and poor outcome among survivors. Stroke 2010;41:54-60.

5 Rizos T, Dorner N, Jenetzky E, Sykora M, Mundiyanapurath S, Horstmann S, Veltkamp R, Rohde S, Bendszus M, Steiner T: Spot signs in intracerebral hemorrhage: Useful for identifying patients at risk for hematoma enlargement? Cerebrovasc Dis 2013;35:582-589.

6 Schoenfeld DA, Richter JR: Nomograms for calculating the number of patients

needed for a clinical trial with survival as an endpoint. Biometrics 1982;38:163-170.

(4)

POWER CALCULATIONS